The Quebec Neuroblastoma (NB) Screening Project was initiated to assess the clinical and biologic aspects of screening infants for the presence of NB in North America. The experimental cohort, all infants born in the province of Quebec during a five year period of time, 5/1/89-4/30/94, are eligible for screening at three weeks and six months of age. Parents mail urine-saturated and dried filter papers to the screening laboratories where the catecholamine metabolites VMA and HVA are assessed by a two-staged screening assay, thin layer chromatography followed by gas chromatography- mass spectrometry. Infants with elevated levels after repeat testing are offered a thorough non-invasive diagnostic evaluation looking for the presence of NB. Patients diagnosed with NB are then uniformly staged, treated, and followed, similar to clinically detected patients either never screened or missed by screening. NB mortality of all children diagnosed as part of the cohort will be compared to results in several population-based, non-screened control groups. Secondary endpoints include NB incidence, clinical staging, and survival. In the process, specific biologic parameters will be studied to determine if known prognostic factors in NBs detected clinically are of equal prognostic importance in preclinically detected tumors; and, importantly, to determine if such studies shed light on the hypothesis that NB is more than one distinct disease. These parameters include tumor N-myc oncogene amplification and expression, DNA content, cytogenetics, gangliosides, and histology; serum ferritin, neuron- specific enolase, and gangliosides; and urinary catecholamine metabolites. Finally, as secondary aims, the effect of preclinical detection of NB on health care costs and the maternal psychosocial consequences of cancer screening in infants will be determined. With 16 months of accrual in the Quebec Project, NB screening has averaged a voluntary compliance of 92% for three week olds and 76% for six month olds. Twenty-one infants screened positive have been referred to a Quebec medical center for evaluation; seven were diagnosed with NB and in 14 no tumor was found. Nine additional patients in the cohort have been diagnosed clinically; five prior to screening at three weeks of age; one at nine months having never been screened; and three diagnosed after negative screens, two with catecholamine non-secreting tumors and one with a secreting tumor. Good prognosis biologic parameters have been noted in the vast majority of cohort cases. To date, the calculated specificity of the screening program is over 99.99% at both three weeks and six months. The sensitivity of the program is currently unknown and awaits further accrual and, most importantly, clinical detection of children in the cohort with time. The results obtained in this study will help determine whether screening of infants for the detection of NB will lead to a reduction in population- based mortality as well as shed light on the biology of this malignancy.